Field of the Invention
The invention generally relates to inhalation therapy. In particular, the invention provides methods and devices for improved dispersion and deagglomeration of dry powders and new formulations therefor.
Background of the Invention
Dry powder inhalers (DPIs) are most efficient at delivering medicines to the lungs when they form aerosols with large numbers of small particles. In conventional DPIs, particles smaller than approximately 5 μm are considered advantageous for efficient lung deposition (Finlay 2001; Newman 2009). For enhanced condensational growth (ECG) or excipient enhanced growth (EEG) delivery, particles with an aerodynamic diameter of approximately 1 μm and below (i.e., submicrometer) are required (Hindle and Longest 2010; Longest et al., 2012a).
The mass fraction of aerosol particles with aerodynamic diameters of 5 μm and below (or 1 μm and below) is quantified as the fine particle fraction; FPF5 μm (or FPF1 μm). The mass median aerodynamic diameter (MMAD) is also used to quantify size, which is defined as the aerodynamic particle size at the 50th percentile of a cumulative mass distribution curve. Increasing the FPF and decreasing the MMAD of pharmaceutical aerosols are critical for improved DPI performance.
A significant disadvantage of particles smaller than 5 μm is that they are often cohesive, especially if micronization has been employed to produce the particles. It is recognized that particle cohesion increases with decreasing particle size. Conventionally, these particles are either agglomerated or blended with larger carrier particles to overcome difficulties in dispersing them in the currently used DPIs. Producing powder formulations that are capable of being dispersed with high efficiency (increasing FPF and decreasing MMAD) using commercially available or novel DPIs is critical to improve delivery to the lungs using the powder inhalation technique.
Current DPI systems deliver only approximately 5-40% of the inhaled aerosol to the lungs, with the remainder depositing in the mouth and throat (Delvadia et al., 2012b; Geller et al., 2011; Longest et al., 2012b; Newman and Busse 2002). Aerosols depositing in the extrathoracic airways increase side effects, increase dose variability, and wastes valuable medication.